Photo courtesy of NIGMS
Researchers say they have identified substantial differences in the procedures and quality of cancer genome sequencing between sequencing centers.
And this led to dramatic discrepancies in the number and types of somatic mutations detected when using the same cancer genome sequences for analysis.
The group’s study involved 83 researchers from 78 institutions participating in the International Cancer Genomics Consortium (ICGC).
The ICGC is an international effort to establish a comprehensive description of genomic, transcriptomic, and epigenomic changes in 50 different tumor types and/or subtypes that are thought to be of clinical and societal importance across the globe.
The consortium is characterizing more than 25,000 cancer genomes and carrying out 78 projects supported by different national and international funding agencies.
For the current project, which was published in Nature Communications, researchers studied a patient with chronic lymphocytic leukemia and a patient with medulloblastoma.
The team analyzed the entire tumor genome of each patient and compared it to the normal genome of the same patient to decipher the molecular causes for these cancers.
The researchers said they saw “widely varying mutation call rates and low concordance among analysis pipelines.”
So they established a reference mutation dataset to assess analytical procedures. They said this “gold-set” reference database has helped the ICGC community improve procedures for identifying more true somatic mutations in cancer genomes and making fewer false-positive calls.
“The findings of our study have far-reaching implications for cancer genome analysis,” said Ivo Gut, of Centro Nacional de Analisis Genómico in Barcelona, Spain.
“We have found many inconsistencies in both the sequencing of cancer genomes and the data analysis at different sites. We are making our findings available to the scientific and diagnostic community so that they can improve their systems and generate more standardized and consistent results.”
